Indian Journal of Chemistry Vol. 40A, December 2001, pp. 1313-1318

Mixed-ligand stability constants of divalent metal ions with glycine and hydroxamic acids

Y K Agrawal*, S K Menon & PC Parekh

Chemistry Department, School of Sciences, Gujarat University, Ahmedabad 380 009, India

Received 16 May 2001; revised 6 September 200/

The thermodynamic mixed ionization constants, pK ~8 of N-m-chlorophenyl-p-substituted benzohydroxamic acids and

glycine have been determined in 0.083 to 0.24 mole fraction of dioxane (n2) 25°C. The mixed pK ~8 are correlated with the

Hammett equation. The determined stability constants have been found to follow the order Pd(II) > Cu(II) > Ni(II) > Zn(ll) > Co(ll) > Fe( II) > Mn(II) and these also follow the order of basicities of the ligands. The linear free-energy relationship for the particular set of metal ions and the set of ligands is calculated and compared.

The role of metal ions indicate the importance of ternary chelates in the activation of enzymes in biological process 1• Metal chelates of hydroxamic acids are known to possess bactericidal, fungicidal and antitubercular activity and some transition metal chelates have now been used in blood preservation 1

·2

.

Similarly, glycine is widely distributed in proteins, it is particularly abundant in gelatin and fibrin. Gycine is also present in bile acids and it contributes to detoxication processes in liver3

. The possibility of formation of mixed-ligand complexes in biological liquids makes it worthwhile to measure the stability of ternary complexes. Mixed chelation occurs commonly in biological fluids. There are large number of the potential ligands likely to compete for metal ions found in V/V04

.

The metal-ligand stability constants of divalent metal ions with hydroxamic acids have been reported elsewhere5

• The present investigation involves the determination of mixed ligand stability constants of Fe(ll), Co(ll), Ni(II), Cu(II), Zn(ll) and Pd(II) with N­m-chlorophenyl-p-substituted benzohydroxamic acids and glycine in 50 volume % dioxane water at 25°C.

The ionization constants of glycine(HA) and hydroxamic acid(HB) can be represented as

... (1)

... (2)

Similarly, the mixed ionization constants of glycine and hydroxamic acid can be expressed as,

KH - [H+] 2 [AB] HAB~ H++AB;

AB- [HAB]

.. . (3)

... (4)

where (HA) and (HB) are in equimolar quantities. The equilibrium constant for the binary complex is

H+B-'" HB· KM = [MB] .....-- , B [M][B]

... (5)

and for ternary complex it is

HB _..A++MAB· KMB = [MAB] .....-- , MAB [HB][A] ... (6)

where B is primary and A is secondary ligand. The difference in stability, ~logK, between the

binary and ternary complexes is one way to characterize the tendency towards the formation of mixed-ligand complexes (6).

~logK = log K ~!8 ~ log K ~8 . .. (7)

Since more co-ordination positions are available for bonding of the first ligand to a given multivalent metal ion than for the second ligand, the stability constants for formation of the 1: 1 complex is usually greater than that of 1: 1: 1 complex vtz.

1314 INDIAN J CHEM, SEC A, DECEMBER 2001

log K~8 > log K~;B and one expects to observe

negative values for ~logK. The overall stability constants for the formation of

a ternary complexes are given by Eqn. (8).

M+B+A ~ MAB · AM = [MAB] , 1-'MAB [M](A][B]

. .. (8)

logK ~!B = logp M -logK ~B MAB

... (9)

For the calculation of stability constants of mixed­ligand complexes a FORT AN V computer programme was used7 The 23 points from the titrations data were taken for the calculation of

logK ~!s and logp M . The average values reported MAB

are of 5 sets of titrations performed with the accuracy of ± 0.03 log unit (2 cr).

Material and Methods All the chemicals used were of AR or GR grades of

BDH or Merck, respectively with the purity of 99.99%.

Reagent The hydroxamic acids were synthesized as

described elsewhere8• Their purity 99.95% was

ascertained by HPLC. Tetrabutylammonium hydroxide (Bu4NOH, 0.1 mol dm-3

) was used as a titrant. This was standardized against potassium hydrogen phthalate9

. The metal perchlorates were prepared from their oxides. The concentrations of stock metal ion solutions were determined volumetrically with standard EDTA9 except Pd(II) which was determines gravimetrically9

• Doubly distilled water was redistilled over alkaline KMn04

and tested for the absence of carbonate. Dioxane was purified as described elsewhere10

•

The digital Radiometer pH meter Model PHM84, equipped with combined glass and ealomel electrode (G4), was used for pH measurements. It was standardized with Radiometer buffers of pH 4 and pH 7 (ref, 11). The pH meter was calibrated by the titration of standard acids using the calibration curve with the accuracy of pH ± 0.002 (ref. 7).

Procedure The titration procedure followed was similar to that

described earlier12• The titration vessel with its

contents was thermostated at (25 ± 0.1 )°C and

nitrogen presaturated by passing through a dioxane­water mixture was bubbled through the solution and the combined electrode was placed in the vessel. The solution was then titrated against 0.1 mol dm -3

tetrabutylammonium hydroxide that too was prepared in the desired dioxane water mixture and noting the pH meter reading after each addition of small aliquots of alkali.

The ionization constant of glycine and the mixed ionization constant of N- aryl hydroxamic acids and glycine were determined at 25°C in 30, 50 and 60 volume % dioxane water. For the mixed ionization constant, weighed quantities of each ligand corresponding to a 0.005 mol dm-1 solution in a final volume of 50 cm3 were used for titration. For the stability constant measurements, the following sets were titrated (1) HC104 (lxi0-3 mol dm- 1

), (2) HCl04 (lxl0-3 mol dm- 1

) + N-aryl hydroxamic acid (lx10-3 mol dm- 1

) + glycine (lx10·3 mol dm· 1 ), (3)

(2) + metal solutions (lxl0-3 mol dm- 1), (4) HC104

(lxl0-3 mol dm- 1 + glycine (2x10-3 mol dm-1) , (5)

HC104 (1x10-3 mol dm- 1) + N-ary! hydroxamic acid

(2x10-3 mol dm· 1 ), (6) (4) + metal solution (lxl0-3

mol dm-1), (7) (5) + metal solutions (lxl0-3 mol

dm- 1). All the titrations were performed at 25°C in 50

volume % dioxane water.

Results and Discussion The thermodynamic mixed ionization constants,

pK~8 of N-m-chlorophenyl-p-substituted benzohy­

droxamic acids and glycine in different dioxane water media at (25 ± 0.1)°C are given in Table 1.

A plot of mixed pK ~B against mole fraction of

dioxane, showed a linear relationship as was observed for substituted hydroxamic acids alone5

. Linear

equations between mixed pK ~6 and mole fraction of

dioxane, (x2), and the respective correlation coefficients are given in Table 1.

The mixed pK ~B follow the order of pKa of p­

substituted hydroxamic acids. The plots of mixed

pK ~B against the pKa were linear and the empirical

relationships are given in Table 2. H Correlation of the mixed pK AB of N-m-

chl0rophenyl-p-substituted benzohydroxamic acid derived from benzoic acid with the Hammet equation

K log-= crp indicate that the mixed experimental

Ko

AGRAWAL et al.: MIXED-LIGAND STABILITY CONSTANT STUDIES 1315

Table !-Ionisation constants of pK~B of chlorophenyl -p-substituted benzohydroxamic acids and glycine in dioxane water at 25°C.

Cl

k N-OH y-, andH2N-CH2COOH

R C=O 0

R, I= C2H50; II. CH30 , III. CH3 , IV. H, V. F, VI. Cl, VII. Br

Compd. R MixedpK pK ~B Mixed pK~B = mx+c

No. mole faction of the dioxane X2 m c 0.083 0.174 0.240

CzH50 9.81 10.70 11.36 9.86 8.99 0.999

II CH30 9.68 10.60 11.26 10.06 8.84 0.999

Ill CH3 9.63 10.55 11.21 10.66 8.79 0.999

IV H 9.54 10.45 11.10 9.94 8.71 0.999

v F 9.41 10.35 11.01 10.19 8.56 0.999

VI Cl 9.25 10.20 10.85 10.20 8.41 0.999

VII Br 9.28 10.20 10.86 10.06 8.44 0.999

a = regression equation r = correlation coefficient

Table 2-Hammet mixed pK. of N-m-chlorophenyl-p-substituted benzohydroxamic acids and glycine in dioxane water at 25°C.

Com pd. R Mole Mixed (J Mixed Mixed pKa No. fraction of pK~s pK~s pK~oi Benzoic

dioxane (X) Expti.(X) Hammet Least Square acid

II CH30 0.083 9.68 -0.268 9.77 9.71 4.47

0.074 10.60 10.66 10.63

0.240 11 .26 11 .31 11.24

III CH3 0.083 9.63 -0.170 9.69 9.59 4.34

0.174 10.55 10.58 10.52

0.240 11.21 11.24 11.15

IV H 0.083 9.54 9.54 9.47 4.21

0.174 10.45 10.45 10.41

0.240 11.10 11.10 11 .06

v F 0.083 9.41 +0.062 9.48 9.40 4.14

0.174 10.35 10.40 10.34

0.240 11.01 11 .05 11.01

VI Cl 0.083 9.25 +0.227 9.34 9.26 3.99

0.174 10.20 10.27 10.21

0.240 10.85 10.92 10.90

Vll Br 0.083 9.28 +0.232 9.33 9.27 4.00

0.174 10.20 10.26 10.22

0.240 10.86 10.91 10.91

x=mole traction of dioxane. pK~s; =Mixed pK~8 obtained from Hammet a function , logK-logK0 =PCJ X=0.083, 8=0.89, X=0.174,

p=0.89; and X=0.240, p=0.80. Mixed pK~Bj' X=0.83, Mexed pK ~8 =0.919+0.560, X=0.74, pK ~8 =0.868R+6.75 and X=0.240,

pK ~6 =0.706R+8.09. (where R+pK0 of sibstituted benzoic acids).

1316 INDIAN J CHEM, SEC A, DECEMBER 2001

Table 3-Thennodynamic mixed-ligand stability constants of divalent metal ions with N-m-chlorophenyl-p··substituted benzohydroxamic acids and glycine in 50 volume % dioxane water at 25°C.

Compd. R pf<!l log KA log KAA log(3 t.log K log X t.log 13 No. AB MA MAB MAB

II

III

IV

v VI

VII

II

Ill

IV

v VI

VII

II

III

IV

v VI

VII

II

III

IV

v VI

VII

II

Ill

IV

v VI

VII

II

CH3

H

F

Cl

Br

C2HsO CH30

CH3

H

F

Cl

Br

C2HsO CH30

CH3

H

F

Cl

Br

C2HsO CH30

CH3

H

F

Cl

Br

C2HsO CH30

CH3

H

F

Cl

Br

10.70

10.60

10.55

10.45

10.35

10.20

10.20

10.70

10.60

10.55

10.45

10.35

10.20

10.20

10.70

10.60

10.55

10.45

10.35

10.20

10.20

10.70

10.60

10.55

10.45

10.35

10.20

10.20

10.70

10.60

10.55

10.45

10.35

10.20

10.20

10.70

10.60

11.91

11.82

11.65

11.47

I 1.34

11.15

II. I 3

11.29

Il.l5

11.00

10.86

10.72

10.52

10.52

8.75

8.60

8.55

8.25

8.1 I

7.91

7.89

8.55

8.35

8.30

8.13

7.99

7.78

7.76

8.45

8.30

8.26

8.09

7.95

7.73

7.71

7.65

7.45

Palladium(II) 10.43

10.24

10.01

9.82

9.64

9.43

9.48

Copper (II)

9.62

9.51

9.25

9.05

8.90

8.60

8.59

Nickel (II)

7.42

7.15

6.97

6.73

6.50

6.30

6.28

Zinc (II)

6.72

6.62

6.48

6.35

6.22

6.01

6.03

Cobalt (II)

6.65

6.57

6.40

6.30

6.17

5.95

5.97 Iron (II)

6.52

6.35

22.34

22.06

21.66

21.29

20.98

20.58

20.61

20.91

20.66

20.25

19.91

19.62

19.12

19.11

16.17

15.75

15.52

14.98

14.61

14.21

14.17

15.27

14.97

14.78

14.48

14.21

13.79

13.79

15.10

14.87

14.66

14.39

14.12

13.68

13.68

14.17

13.80

-0.56

-0.66

-0.65

-0.73

-0.78

-0.80

-0.72

-0.75

-0.77

-0.80

-0.89

-0.90

-1 .01

-1.01

-0.37

-0.50

-0.41

-0.48

-0.57

-0.56

-0.56

-1.53

-1.45

-1.32

-1.15

-1.14

-1.15

-1.10

-1.17

-1.09

-1.01

-0.94

-0.93

-0.93

-0.89

-0.35

-0.35

5.97

5.67

5.33

4.95

4.59

4.19

4.21

6.12

5.89

5.57

5.23

4.93

4.32 1

4.31

4.74

4.24

4.25

3.51

3.04

2.65

2.60

2.79

2.52

2.66

2.61

2.36

1.92

1.98

4.14

3.99

4.07

3.90

3.63

3.17

3.19

4.59

4.22

2.68

2.53

2.36

2.17

1.99

1.79

1.80

2.76

2.64

2.48

2.31

2.16

.86

1.85

2.07

1.82

1.82

1.45

1.22

1.02

1.00

1.09

0.96

1.03

1.00

0.88

0.66

0.69

1.77

1.69

1.73

1.65

1.51

1.28

1.29

1.99

1.81 Contd--

AGRAWAL et al. : MIXED-LIGAND STABILITY CONSTANT STUDIES 1317

Table 3-Thermodynamic mixed-ligand stability constants of divalent metal ions with N-m-chlorophenyl-p-substituted benzohydroxamic acids and glycine in 50 volume % dioxane water at 25°C-Contd

Com pd. R p~ log K"' log JC"'A logl3 ~log K log X ~log 13 No. AB MA MAB MAB

III CH3 10.55 7.37 6.22 13.59 -0.23 4.35 1.87

IV H 10.45 7.07 5.96 13.93 -{).19 3.79 1.59

v F 10.35 6.92 5.81 12.73 -D.19 3.49 1.44

VI C1 10.20 6.72 5.67 12.33 -{).19 3.09 1.24

VII Br 10.20 6.68 5.57 12.25 -0.19 3.01 1.20

Manganese (II)

C2H50 10.70 7.50 6.33

II CH30 10.60 7.30 6.50

III CH3 10.55 7.15 6.05

IV H 10.45 6.92 5.85

v F 10.35 6.78 5.68

VI C1 10.20 6.56 5.48

VII Br 10.20 6.55 5.45

pK ~8 values and the values calculated by the

Hammett equation are in good agreement. A plot of

mixed pK ~8 in 30, 50 and 60 volume % dioxane

water at 25°C against Hammett a-function is linear and the data are given in Table 2.

The thermodynamic mixed ligand metal stability constants of N - aryl hydroxamic acids and glycine with Pd(II), Fe(II), Co(ll), Ni(II), Cu(II) and Zn(II) in 50 volume % dioxane water at 25°C are given in Table 3. These stability constants were calculated using the pK. of glycine determined at the same conditions which gave the value (10.27±0.02).

The stability constants of binary complexes of glycine follow the order of stability,

Pd(II) > Cu(II)> Ni(II)>Zn(II)>Co(II) >Fe(II)>Mn(II) with logK1 1 0.45>9.65> 7 .417>6.98>6.65>6.00>5.85 and

A similar order is obtained with the mixed ligand metal stability constants which form a ternary complex of the ratio M : A : B to 1 : 1 : 1.

Pd(II) > Cu(Il) >Ni(II)> Zn(II)>Co(II)>Fe(II)>Mn(II) LogK2 7.78> 6.98> 6.40 > 5.97 > 5.54 > 5.08 > 74.98, respectively.

The formation of ternary complex was confirmed from the shape of the pH titration curves7

. It has also been observed that hydrolysis occurs in the ternary chelates at higher pH values than in the case of binary chelates which supports the formation of a ternary

13.83 -0.37 4.56 1.98

13.50 -{).29 4.28 1.84

13.20 -{).20 1.17 1.78

12.77 -{).17 3.78 !.59

12.46 -{).20 3.44 1.42

12.04 -{).19 3.01 1.20

12.00 -0.19 2.99 1.19

chelate in solution 7•11

• The average number of ligand bound per metal, n , values are in the range of 0.25 to 1.95 for all metal ions indicating the formation of 1:1 and finally 1:2 complexes. The stability constants are accurate to ± 0.03 log units (2 cr).

A linear relationship exists between the logarithms of the stability constants of a series of mixed complexes derived from one metal ion with a set of closely related ligands and the pKa values of the same ligands (5 , 12-16) On the basis of this, it is expected that more basic ligands should form more stable complexes. In the case of ternary complexes of N-aryl hydroxamk acids and glycine, a linear relationship

exists between the mixed pK ~8 and

logK~~6 or log~~AB for all systems. It is evident from

the mixed pK ~6 values of hydroxarnic acids and

successive stability constants of the corresponding metal ternary complexes (Tables 1-3) that the introduction of a substituent in the para position has a

similar effect on the mixed pK ~8 p.K ~8 and ternary

stability constant as the order OC2 H5 > OCI-h> CH3>

F > Cl > Br is valid for pK ~8 , and log~~AB. The stabilities of Zn(II)-hydroxamate chelates are

higher than Ni(II)-hydroxamate chelates 12- '

4·16whereas

with the mixed ligands (glycine+ hydroxamic acids) the stabilities of Ni(II) chelates are higher than Zn(II) chelates. This interchange of order may be due to the in the relative preference of mutual ions towards the donors atoms 15

• It has been established'2·15 that

ligands having the nitrogen atom or oxygen atoms as

1318 INDIAN J CHEM, SEC A, DECEMBER 2001

2. 1

1.9

ro 1.7

1. 5

1.3

Pd / ro Cu

2 .0 -1.0 0.0 1.0

e 2.0

Fig. !-Plot of B versus 8

0 Ni

3 .0

Fe 0

t.An

4.0

donors are found to form stronger complexes with a ligand-sensitive metal like Ni(II) while ligands carrying negatively charged oxygen ions form stronger chelates with a ligand in sensitive metal ion like Zn(II), especially for 0-groups. The glycine has the nitrogen atom as donor, forms stronger complexes with Ni(II) compared to Zn(II) whereas hydroxarnic acids having the functional grouping

OH 0 I II

- N- C- form stronger complexes with Zn(II).

The parameters ~logK" the difference between the stability of binary and ternary complexes, logX, the disproportionation constant and ~IogB. the stabilisation constants are given in Table 3. Both ~IogB and logX values are positive in all the cases showing that the influence of both ligands in the ternary complex is mutual and of the same size.

The values of the parameter B calculated 12•16

-18 are

Pd2+ ( 1.546), Cu2+(1.534 ), Ni2+(1 . 760), Zn2+(1.524) Co2+ (1.468), Fe2+ (1.920) and Mn2+ (1.870). The vales of C for compounds 1-VII with the substituents are: H(LOOO), C2H50 (0.975), CH30(0.996), CH3(0.978), F(L002) CI(L006) and Br(L009). The goodness of the fit for the series is shown in Figs 1 and 2. All the values of B and C are found to be

1 .02 r-----------------.

u 0.99

F 0

(J

0 CH

Crl 0 J

0

J

Fig. 2-Plot of C versus cr

comparable, with a correlation coefficient of unity, irrespective of metal ion or ligand compared.

Acknowledgement Financial assistance received from DST, New

Delhi, and Royal Society of Chemistry, London is gratefully acknowledged.

References I Kaim W & Schwcderski B, Bioinorganic chemistry (New

York) 1994. 2 Niemeyer H M & Perez F J, Acs Symp Ser, 582 ( 1995) 260. 3 Zuby G L, Parson W W & Vance D E, Principles of

biochemistry (Wm C Brown England) (1994). 4 Bertini, I, Gray H B, Lippard, S J & Valentine J S (Viva

Books Private Limited, New Delhi) 1998. 5 Parekh P C & Agrawal Y K, J chem Soc, Perkin Trans I I,

(1987) 479. 6 Sigel H & Griesser R, Helv chim Acta, 50, ( 1967) 1842, cf. p.

Chimica, 21 (1967) 489. 7 Martell A E & Motekaitis R J, 2nd Edn (VCH Weinheim,

Germany) (1992). 8 Agrawal Y K, Fullerene Sc. Tech., 5, 275 (1997). 9 Jeffery, G H, Basset J, Mendham J & Danney R C, Vogels

Text book of quantitative chemical analysis, 5'h Edn (Longman, UK) 1989.

10 Armarego, W I F & Perrin D D, Purification of laboratory chemicals, 4'h Edn (Butterworth, Oxford) (1999).

II Perrin D D & Dempsey B, Buffers for pH and metal ion control (Chapman and Hall), 1979.

12 Agrawal Y K, Rus Chern Rev, 48 (1979) 948. 13 Agrawal Y K & Tandon S G, J inorg nucl Chern, 34 (1972)

1291 . 14 Menon S K & Agrawal Y K, Trans met Chern , 8 ( 1983) 292. 15 Irving H & Rossotti H S, J chem Soc, 29 10 (1 954). 16 Parekh PC, Menon S K & Agrawal Y K. J chem Soc, Perkin

Trans I I, ( 1989) II I 7. 17 Menon S K & Agrawal Y K, Rev /norg Chem, 16 (1996) I. 18 Nieboer E & Me Bryde W A E, Can J Chern, 48 ( 1970)

2549.